Scientists are continually researching for effective free radical trapping compounds, known as "spin-traps," since free radicals are believed to be involved in disease initiation and mediation in animals. Ischemia and inflammation are two examples of biological events in which free radicals have been implicated. Spin traps are important for diagnostic and therapeutic purposes. Known spin-traps shown to be effective in animal models include .alpha.-phenyl N-tert-butyl nitrone (PBN), .alpha.-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN), 2-methyl-2-nitrosopropane (MNP), and 5,5 dimethyl-1-pyrroline N-oxide (DMPO).
Despite the discovery of several spin-trap molecules, the need remains for additional compounds which are of increased stability and which work more effectively to trap free radicals in biological systems. There has long been a desire for a stable spin-trap agent, resistant to dimerization, which is lipophilic in nature to increase mobility in and out of cell membranes and which does not have a toxic functionality. It has also been desired to obtain spin-trap agents which trap free radicals faster than known agents.
Another problem in the art has been that proposed structures of desired spin-traps, which theoretically may provide some of the desired properties, are postulated from time to time, but synthesis has been difficult or impossible by known methods. It therefore has been desired that a convenient method of synthesis be available for a spin-trap agent having some or all of the above-described properties.
A further problem in the art has been that, normally, spin trap adducts (formed when the spin trap agent traps a free radical) cannot be directly studied by NMR methods. Adducts must be first reduced as with hydrazine and the hydroxylamine reduction product analyzed. The inability to directly detect spin trap adducts has hampered biological research into the effectiveness of spin-traps as drugs for trapping free-radicals and monitoring therapy.